title: Reduction in RNA levels rather than retardation of translation is responsible for the inhibition of major histocompatibility complex class I antigen presentation by the glutamic acid-rich repeat of herpesvirus saimiri open reading frame 73.
abstract: Herpesvirus saimiri (HVS) establishes a persistent infection in squirrel monkeys by maintaining its episome within T lymphocytes. The product of open reading frame 73 (ORF73) plays a key role in episomal maintenance and is the functional homologue of Epstein-Barr virus EBNA1 and Kaposi's sarcoma-associated herpesvirus LANA1 proteins. There is little sequence homology among these proteins, although all contain a central domain of repeating amino acids. The repeat domains of EBNA1 and LANA1 enhance the stability of these proteins and cause a retardation in self-protein synthesis, leading to poor recognition by CD8(+) cytotoxic T lymphocytes (CTL). The HVS ORF73 repeat domain is composed of a glutamic acid and glycine repeat linked to a glutamic acid and alanine repeat (EG-EA repeat). Here we show that the EG-EA repeat similarly causes a reduction in the recognition of ORF73 by CD8(+) CTL. However, deletion of the EG-EA repeat from HVS ORF73 had no affect on the stability of the protein or its rate of translation. In contrast, the presence of the EG-EA repeat was found to decrease the steady-state levels of ORF73 mRNA. The inhibitory properties of the EG-EA repeat were maintained when transferred to a heterologous protein, and manipulation of the repeat revealed that the motif EEAEEAEEE was sufficient to cause a reduction in recognition of ORF73 by CD8(+) CTL. Thus, the EG-EA repeat of HVS ORF73 plays a role in immune evasion but utilizes a mechanism distinct from that of the EBNA1 and LANA1 repeats.
authors.affiliation: Division of Medical Microbiology, University of Liverpool, 8th Floor Duncan Building, Daulby Street, Liverpool L69 3GA, United Kingdom.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Gao
authors.forename: Judy M
authors.initials: JM
authors.lastname: Coulson
authors.forename: Adrian
authors.initials: A
authors.lastname: Whitehouse
authors.forename: Neil
authors.initials: N
authors.lastname: Blake
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006567:Herpesvirus 2, Saimiriine / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis*; D012367:RNA, Viral / Q000096:biosynthesis*; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins